Nicotinic acid induces antinociceptive and anti-inflammatory effects in different experimental models.

Although in vitro studies have shown that nicotinic acid inhibits some aspects of the inflammatory response, a reduced number of in vivo studies have investigated this activity. To the best of our knowledge, the effects induced by nicotinic acid in models of nociceptive and inflammatory pain are not known. Per os (p.o.) administration of nicotinic acid (250, 500 or 1000 mg/kg, -1 h) inhibited the first and the second phases of the nociceptive response induced by formalin in mice. Nicotinic acid (250 or 500 mg/kg, -1 and 3 h) also inhibited the mechanical allodynia induced by carrageenan in rats, a model of inflammatory pain. However, in a model of nociceptive pain, exposure of mice to a hot-plate, nicotinic acid was devoid of activity. In addition to inhibiting the nociceptive response in models of inflammatory pain, nicotinic acid (250 or 500 mg/kg, p.o., -1 and 3 h) inhibited paw edema induced by carrageenan in mice and rats. Picolinic acid (62.5 or 125 mg/kg, p.o., -1 h), a nicotinic acid isomer, inhibited both phases of the nociceptive response induced by formalin, but not paw edema induced by carrageenan in mice. The other nicotinic acid isomer, isonicotinic acid, was devoid of activity in these two models. In conclusion, our results represent the first demonstration of the activity of nicotinic acid in experimental models of nociceptive and inflammatory pain and also provide further support to its anti-inflammatory activity. It is unlikely that conversion to nicotinamide represents an important mechanism to explain the antinociceptive and anti-inflammatory activities of nicotinic acid. The demonstration of new activities of nicotinic acid, a drug that has already been approved for clinical use and presents a positive safety record, may contribute to raise the interest in conducting clinical trials to investigate its usefulness in the treatment of painful and inflammatory diseases.

Characterization of the antinociceptive and anti-inflammatory activities of doxycycline and minocycline in different experimental models.

Tetracyclines induce anti-inflammatory effects unrelated to their antimicrobial activities. We investigated the effect induced by minocycline and doxycycline in models of nociceptive and inflammatory pain, edema, fever, cell migration and formation of fibrovascular tissue, as these effects have not been fully investigated. Tetracyclines were administered via intraperitoneal route 1 h before the tests. Minocycline and doxycycline (100 mg/kg) inhibited the second phase of the formalin-induced nociceptive response in mice. Doxycycline (100 mg/kg) also inhibited the first phase. The nociceptive response induced by phorbol 12,13-didecanoate (PDD) in mice was inhibited by doxycycline (100 mg/kg). Furthermore, carrageenan-induced mechanical allodynia in rats was inhibited by doxycycline and minocycline (50 or 100 mg/kg). However, they did not enhance the latency in the hot-plate test. It is unlikely that antinociception resulted from motor incoordination or muscle relaxing effect, as both tetracyclines (100 mg/kg) did not impair the motor activity of mice in the rota-rod test. Doxycycline (50 or 100 mg/kg) or minocycline (50 or 100 mg/kg) inhibited carrageenan-induced paw edema in rats. However, only minocycline (100 mg/kg) inhibited PDD-induced edema. Carrageenan-induced leukocyte migration into the peritoneal cavity of rats was inhibited by both tetracyclines (100 mg/kg). Endotoxin-induced fever in rats was also inhibited by doxycycline (50 or 100 mg/kg) or minocycline (100 mg/kg). Finally, formation of fibrovascular tissue induced by subcutaneous implant of a cotton pellet in mice was inhibited by a 6-day administration of both tetracyclines (50 or 100 mg/kg day). Concluding, this study clearly shows the antinociceptive and anti-inflammatory activities of these second-generation tetracyclines.